Study of MK-4830 as Monotherapy and in Combination With Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-4830-001)

NCT03564691 | Completed Phase 1 FDA Drug

• 5 other identifiers: 4830-001MK-4830-0012023-509542-35-00U1111-1300-19522019-003164-53
• Study Type: interventional
• Target: 470
• Locations: 12 countries
• Sites: 37

Brief Summary

This study consists of several parts: dose escalation, dose expansion, dose expansion in Chinese participants residing in China, and coformulation. Dose escalation is to evaluate the safety, tolerability, and preliminary efficacy of MK-4830 monotherapy administration (Arms A and B) and in combination with pembrolizumab (Arm C). Dose expansion is to evaluate the objective response rate (ORR) of MK-4830 in combination with pembrolizumab (Arms A-F); evaluate the safety and tolerability of MK-4830 administered in combination with pembrolizumab, carboplatin, and pemetrexed (Arm G) and of MK-4830 administered in combination with pembrolizumab and lenvatinib (Arm H); evaluate the safety, tolerability and ORR of MK-4830 in combination with pembrolizumab plus chemotherapy (Arms I-L); and evaluate the safety and tolerability of MK-4830 in combination with pembrolizumab in Chinese participants from China (Arm M). The coformulation part (Arm N) evaluates the safety and tolerability of MK-4830A (coformulation of MK-4830 800 mg + pembrolizumab 200 mg). There is no formal hypothesis testing in this study.

Conditions

Neoplasms

Keywords

PD1; PD-1; PDL1; PD-L1

Outcome Measures

Primary Outcomes (5)

• Dose-Limiting Toxicities (DLTs)

  The occurrence of the following toxicities, if assessed by the investigator to be possibly, probably, or definitely related to study treatment administration: * Grade 4 nonhematologic toxicity (not laboratory) * Grade 4 hematologic toxicity lasting \>=7 days, except thrombocytopenia: * Any nonhematologic AE \>=Grade 3 in severity, with exceptions * Any Grade 3 or Grade 4 alanine aminotransferase, aspartate aminotransferase, and/or bilirubin laboratory value * Any other nonhematologic laboratory value if: Clinically significant medical intervention is required to treat the participant, OR The abnormality leads to hospitalization, OR The abnormality persists for \>1 week, OR The abnormality results in a drug-induced liver injury * Febrile neutropenia Grade 3 or Grade 4 * Prolonged delay (\>2 weeks) in initiating Cycle 2 due to treatment-related toxicity. * Any treatment-related toxicity that causes the participant to discontinue treatment during Cycle 1. * Grade 5 toxicity

  Cycle 1 (Up to 21 days)

• Number of Participants Who Experienced an Adverse Event (AE)

  An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. The number of participants who experienced an AE will be presented.

  Up to approximately 27 months

• Number of Participants Who Discontinued Study Treatment Due to an AE

  An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. The number of participants who discontinued study treatment due to an AE will be presented.

  Up to approximately 24 months

• Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or Response Assessment in Neuro-Oncology (RANO) as Assessed by Investigator

  For Arms A, C-F, I, and K ORR is defined as the percentage of participants who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. For Arm B, ORR is defined as the percentage of participants who experience a PR or CR per RANO, determined by: disappearance or size reduction of lesions, and review of abnormalities on fluid-attenuated inversion recovery (T2/FLAIR) images; Clinical status based on age-adjusted performance; And whether daily steroid dose has changed since previous visit. The percentage of participants who experience a CR or PR based on modified RECIST 1.1 as assessed by investigator or based on RANO will be presented.

  Up to approximately 24 months

• ORR per Modified RECIST (mRECIST) 1.1 as Assessed by Investigator

  Per protocol, ORR per mRECIST 1.1 will be reported for Arm L participants. ORR is defined as percentage of participants who have CR (disappearance of all pleural \& non-pleural disease) or PR (summed measurement (SM) decrease by at least 30% from baseline scan SM) per mRECIST 1.1. The percentage of participants who experience CR or PR based on mRECIST 1.1 as assessed by investigator will be presented.

  Up to approximately 24 months

Secondary Outcomes (6)

• Area Under the Curve (AUC) of Plasma MK-4830

  At designated time points detailed in Description (Up to approximately 25 months)

• Minimum Concentration Between Doses (Ctrough) of Plasma MK-4830

  At designated time points detailed in Description (Up to approximately 25 months)

• Maximum Drug Concentration (Cmax) of Plasma MK-4830

  At designated time points detailed in Description (Up to approximately 25 months)

• Number of Participants Positive for Anti-Drug Antibodies (ADA) After MK-4830 plus Pembrolizumab Treatment

  At designated time points (Up to approximately 25 months)

• Minimum Concentration Between Doses (Ctrough) of Plasma Pembrolizumab in Arm M

  At designated time points detailed in Description (Up to approximately 25 months)

Study Arms (17)

Dose Escalation, Part A: MK-4830 Monotherapy

EXPERIMENTAL

MK-4830 monotherapy (with MK-4830 doses determined by an accelerated titration design \[ATD\]) will be administered intravenously (IV), every 3 weeks (Q3W), starting with Cycle 1, Day 1, for a maximum of 35 cycles (up to approximately 2 years). Each cycle is 21 days. Participants enroll with histologically or cytologically confirmed pancreatic adenocarcinoma.

Drug: MK-4830

Dose Escalation, Part B: MK-4830 Monotherapy

EXPERIMENTAL

MK-4830 monotherapy (with MK 4830 doses determined by a modified toxicity probability interval \[mTPI\] method) will be administered IV, Q3W, starting with Cycle 1, Day 1, for a maximum of 35 cycles (up to approximately 2 years). Each cycle is 21 days. Participants enroll with histologically or cytologically confirmed pleural or peritoneal malignant mesothelioma, epithelial, sarcomatoid, or biphasic subtypes.

Drug: MK-4830

Dose Escalation, Part C: MK-4830 and Pembrolizumab

EXPERIMENTAL

Combination therapy with MK-4830 and pembrolizumab (with MK-4830 doses determined by an mTPI design). MK-4830 will be administered IV following pembrolizumab infusion, Q3W, starting with Cycle 1, Day 1, for a maximum of 35 cycles. Each cycle is 21 days. Pembrolizumab will be administered by IV, Q3W, starting with Cycle 1, Day 1. Each cycle is 21 days. The combination may be administered for a maximum of 35 cycles (up to approximately 2 years).

Drug: MK-4830; Drug: Pembrolizumab

Dose Expansion, Arm A: Pancreatic Adenocarcinoma

EXPERIMENTAL

Combination therapy with the preliminary recommended phase 2 dose (RP2D) A of MK-4830, and pembrolizumab, in participants with histologically or cytologically confirmed pancreatic adenocarcinoma. MK-4830 will be administered IV following pembrolizumab infusion, Q3W, starting with Cycle 1, Day 1, for a maximum of 35 cycles. Each cycle is 21 days. Pembrolizumab will be administered by IV, Q3W, starting with Cycle 1, Day 1. Each cycle is 21 days. The combination may be administered for a maximum of 35 cycles (up to approximately 2 years).

Drug: MK-4830; Drug: Pembrolizumab

Dose Expansion, Arm B: Glioblastoma (GBM)

EXPERIMENTAL

Combination therapy with the preliminary RP2D A of MK-4830, and pembrolizumab, in participants with histologically or cytologically confirmed GBM. MK-4830 will be administered IV following pembrolizumab infusion, Q3W, starting with Cycle 1, Day 1, for a maximum of 35 cycles. Each cycle is 21 days. Pembrolizumab will be administered by IV, Q3W, starting with Cycle 1, Day 1. Each cycle is 21 days. The combination may be administered for a maximum of 35 cycles (up to approximately 2 years).

Drug: MK-4830; Drug: Pembrolizumab

Dose Expansion, Arm C: R/M HNSCC

EXPERIMENTAL

Combination therapy with the preliminary RP2D A of MK-4830, and pembrolizumab, in participants who have histologically or cytologically-confirmed recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) whose disease progressed on an anti-programmed cell death 1/programmed cell death ligand 1 (PD1/L1) therapy. MK-4830 will be administered IV following pembrolizumab infusion, Q3W, starting with Cycle 1, Day 1, for a maximum of 35 cycles. Each cycle is 21 days. Pembrolizumab will be administered by IV, Q3W, starting with Cycle 1, Day 1. Each cycle is 21 days. The combination may be administered for a maximum of 35 cycles (up to approximately 2 years).

Drug: MK-4830; Drug: Pembrolizumab

Dose Expansion, Arm D: PD-L1 positive HNSCC, Dose A

EXPERIMENTAL

Combination therapy with the preliminary RP2D A of MK-4830, and pembrolizumab, in participants who have histologically or cytologically-confirmed advanced programmed death-ligand 1 (PD-L1) positive head and neck squamous cell carcinoma (HNSCC). MK-4830 will be administered IV following pembrolizumab infusion, Q3W, starting with Cycle 1, Day 1, for a maximum of 35 cycles. Each cycle is 21 days. Pembrolizumab will be administered by IV, Q3W, starting with Cycle 1, Day 1. Each cycle is 21 days. The combination may be administered for a maximum of 35 cycles (up to approximately 2 years).

Drug: MK-4830; Drug: Pembrolizumab

Dose Expansion, Arm E: First-Line Advanced NSCLC, Dose A

EXPERIMENTAL

Combination therapy with the preliminary RP2D A of MK-4830, and pembrolizumab, in participants who have histologically-confirmed, first-line treatment advanced non-small-cell-lung-cancer (NSCLC) (Stage IIIB or IV). MK-4830 will be administered IV following pembrolizumab infusion, Q3W, starting with Cycle 1, Day 1, for a maximum of 35 cycles. Each cycle is 21 days. Pembrolizumab will be administered by IV, Q3W, starting with Cycle 1, Day 1. Each cycle is 21 days. The combination may be administered for a maximum of 35 cycles (up to approximately 2 years).

Drug: MK-4830; Drug: Pembrolizumab

Dose Expansion, Arm F: First-Line Advanced NSCLC, Dose B

EXPERIMENTAL

Combination therapy with the preliminary RP2D B of MK-4830, and pembrolizumab, in participants who have histologically-confirmed, first-line treatment advanced non-small-cell-lung-cancer (NSCLC) (Stage IIIB or IV). MK-4830 will be administered IV following pembrolizumab infusion, Q3W, starting with Cycle 1, Day 1, for a maximum of 35 cycles. Each cycle is 21 days. Pembrolizumab will be administered by IV, Q3W, starting with Cycle 1, Day 1. Each cycle is 21 days. The combination may be administered for a maximum of 35 cycles (up to approximately 2 years).

Drug: MK-4830; Drug: Pembrolizumab

Dose Expansion, Arm G: NSCLC, +Carboplatin/Pemetrexed

EXPERIMENTAL

Combination therapy with the preliminary RP2D A of MK-4830, pembrolizumab, and carboplatin/pemetrexed in participants with advanced non-squamous non-small-cell-lung-cancer (NSCLC) (Stage IIIB or IV). MK-4830 will be administered IV following pembrolizumab infusion, Q3W, starting with Cycle 1, Day 1, for a maximum of 35 cycles. Each cycle is 21 days. Pembrolizumab will be administered by IV, Q3W, starting with Cycle 1, Day 1. Each cycle is 21 days. The combination may be administered for a maximum of 35 cycles. Carboplatin and pemetrexed will be administered IV Q3W, starting with Cycle 1, Day 1, for 4 cycles, followed by pemetrexed Q3W continuous with MK-4830 and pembrolizumab, up to 35 cycles. Each cycle is 21 days (up to approximately 2 years).

Drug: MK-4830; Drug: Pembrolizumab; Drug: Carboplatin; Drug: Pemetrexed

Dose Expansion, Arm H: RCC, +Lenvatinib

EXPERIMENTAL

Combination therapy with the preliminary RP2D A of MK-4830, pembrolizumab, and lenvatinib in participants with advanced renal cell carcinoma (RCC). MK-4830 will be administered IV, Q3W, starting with Cycle 1 following pembrolizumab infusion, Day 1, for a maximum of 35 cycles. Each cycle is 21 days. Pembrolizumab will be administered by IV, Q3W, starting with Cycle 1, Day 1. Each cycle is 21 days. The combination may be administered for a maximum of 35 cycles (up to approximately 2 years). Lenvatinib will be administered orally once daily for up to 35 cycles of 21 days (up to approximately 2 years).

Drug: MK-4830; Drug: Pembrolizumab; Drug: Lenvatinib

Dose Expansion, Arm I: R/M Gastric/GE Junction Adenocarcinoma

EXPERIMENTAL

Combination therapy with the preliminary RP2D A of MK-4830, and pembrolizumab, in participants who have histologically or cytologically-confirmed recurrent or metastatic (R/M) gastric or gastroesophageal (GE) junction adenocarcinoma and who have been previously treated with at least 2 prior lines of therapy. MK-4830 will be administered IV following pembrolizumab infusion, Q3W, starting with Cycle 1, Day 1, for a maximum of 35 cycles. Each cycle is 21 days. Pembrolizumab will be administered by IV, Q3W, starting with Cycle 1, Day 1. Each cycle is 21 days. The combination may be administered for a maximum of 35 cycles (up to approximately 2 years).

Drug: MK-4830; Drug: Pembrolizumab

Dose Expansion, Arm J: Ovarian Cancer

EXPERIMENTAL

Triple combination therapy with pembrolizumab plus preliminary RP2D A of MK-4830 plus paclitaxel in participants who have histologically confirmed, ovarian cancer. MK-4830 will be administered IV following pembrolizumab infusion, Q3W, starting with Cycle 1, Day 1, for a maximum of 35 cycles. Each cycle is 21 days. Pembrolizumab will be administered by IV, Q3W, starting with Cycle 1, Day 1 for a maximum of 35 cycles (up to approximately 2 years). Each cycle is 21 days. Paclitaxel will be administered by IV, once every week (QW) on Days 1, 8, and 15 of each 21-day cycle until disease progression or prohibitive toxicity.

Drug: MK-4830; Drug: Pembrolizumab; Drug: Paclitaxel

Dose Expansion, Arm K: Triple negative Breast Cancer (TNBC)

EXPERIMENTAL

Triple combination therapy with pembrolizumab plus preliminary RP2D A of MK-4830 plus paclitaxel in participants who have histologically confirmed TNBC. MK-4830 will be administered IV following pembrolizumab infusion, Q3W, starting with Cycle 1, Day 1, for a maximum of 35 cycles. Each cycle is 21 days. Pembrolizumab will be administered by IV, Q3W, starting with Cycle 1, Day 1 for a maximum of 35 cycles (up to approximately 2 years). Each cycle is 21 days. Paclitaxel will be administered by IV on Days 1, 8, and 15 every 4 weeks (Q4W) until disease progression or prohibitive toxicity.

Drug: MK-4830; Drug: Pembrolizumab; Drug: Paclitaxel

Dose Expansion, Arm L: Mesothelioma

EXPERIMENTAL

Triple combination therapy with pembrolizumab plus preliminary RP2D A of MK-4830 plus pemetrexed plus cisplatin in participants who have histologically confirmed advanced mesothelioma. MK-4830 will be administered IV following pembrolizumab infusion, Q3W, starting with Cycle 1, Day 1, for a maximum of 35 cycles. Each cycle is 21 days. Pembrolizumab will be administered by IV, Q3W, starting with Cycle 1, Day 1 for a maximum of 35 cycles (up to approximately 2 years). Each cycle is 21 days. Pemetrexed will be administered by IV, on Day 1 of each Q3W cycle for a maximum of 6 cycles. Each cycle is 21 days. Cisplatin will be administered by IV, on Day 1 of each Q3W cycle for a maximum of 6 cycles. Each cycle is 21 days.

Drug: MK-4830; Drug: Pembrolizumab; Drug: Pemetrexed; Drug: Cisplatin

Dose Expansion, Arm M: Advanced Solid Tumor in Chinese Participants In China

EXPERIMENTAL

Combination therapy with the preliminary RP2D A of MK-4830, and pembrolizumab, in Chinese participants, who reside in China, have histologically or cytologically-confirmed advanced/metastatic solid tumor, and who have been previously treated with at least 2 prior lines of therapy. MK-4830 will be administered IV following pembrolizumab infusion, Q3W, starting with Cycle 1, Day 1, for a maximum of 35 cycles. Each cycle is 21 days. Pembrolizumab will be administered by IV, Q3W, starting with Cycle 1, Day 1. Each cycle is 21 days. The combination may be administered for a maximum of 35 cycles (up to approximately 2 years).

Drug: MK-4830; Drug: Pembrolizumab

Coformulation Phase, Arm N: MK-4830A (Coformulation of MK-4830 + pembrolizumab)

EXPERIMENTAL

Monotherapy with MK-4830A, a coformulation of MK-4830 800 mg + pembrolizumab 200 mg, in participants with histologically or cytologically-confirmed advanced/metastatic solid tumor, and who and have received, been intolerant to, been ineligible for, or refused all treatment known to confer clinical benefit. MK-4830A will be administered IV, Q3W, starting with Cycle 1, Day 1, for a maximum of 35 cycles (up to approximately 2 years). Each cycle is 21 days.

Biological: MK-4830A

Interventions

MK-4830 DRUG

MK-4830 will be administered intravenously (IV) Q3W. In Part C, MK-4830 will be administered after completion of pembrolizumab infusion. Dose escalation will proceed based on emerging safety and tolerability data of MK-4830 as monotherapy (Part A and B) and as combination therapy with pembrolizumab (Part C). For each dose level, an assessment will be made of the safety and tolerability data in order to define the next dose level to be tested.

Dose Escalation, Part A: MK-4830 Monotherapy; Dose Escalation, Part B: MK-4830 Monotherapy; Dose Escalation, Part C: MK-4830 and Pembrolizumab; Dose Expansion, Arm A: Pancreatic Adenocarcinoma; Dose Expansion, Arm B: Glioblastoma (GBM); Dose Expansion, Arm C: R/M HNSCC; Dose Expansion, Arm D: PD-L1 positive HNSCC, Dose A; Dose Expansion, Arm E: First-Line Advanced NSCLC, Dose A; Dose Expansion, Arm F: First-Line Advanced NSCLC, Dose B; Dose Expansion, Arm G: NSCLC, +Carboplatin/Pemetrexed; Dose Expansion, Arm H: RCC, +Lenvatinib; Dose Expansion, Arm I: R/M Gastric/GE Junction Adenocarcinoma; Dose Expansion, Arm J: Ovarian Cancer; Dose Expansion, Arm K: Triple negative Breast Cancer (TNBC); Dose Expansion, Arm L: Mesothelioma; Dose Expansion, Arm M: Advanced Solid Tumor in Chinese Participants In China

Pembrolizumab DRUG

Pembrolizumab will be administered at 200 mg IV Q3W.

Also known as: MK-3475, SCH 900475, KEYTRUDA®

Dose Escalation, Part C: MK-4830 and Pembrolizumab; Dose Expansion, Arm A: Pancreatic Adenocarcinoma; Dose Expansion, Arm B: Glioblastoma (GBM); Dose Expansion, Arm C: R/M HNSCC; Dose Expansion, Arm D: PD-L1 positive HNSCC, Dose A; Dose Expansion, Arm E: First-Line Advanced NSCLC, Dose A; Dose Expansion, Arm F: First-Line Advanced NSCLC, Dose B; Dose Expansion, Arm G: NSCLC, +Carboplatin/Pemetrexed; Dose Expansion, Arm H: RCC, +Lenvatinib; Dose Expansion, Arm I: R/M Gastric/GE Junction Adenocarcinoma; Dose Expansion, Arm J: Ovarian Cancer; Dose Expansion, Arm K: Triple negative Breast Cancer (TNBC); Dose Expansion, Arm L: Mesothelioma; Dose Expansion, Arm M: Advanced Solid Tumor in Chinese Participants In China

Carboplatin DRUG

Carboplatin will be administered IV Q3W.

Also known as: Paraplatin

Dose Expansion, Arm G: NSCLC, +Carboplatin/Pemetrexed

Pemetrexed DRUG

Pemetrexed will be administered IV Q3W.

Also known as: ALIMTA®, Pleumet, Pemecad

Dose Expansion, Arm G: NSCLC, +Carboplatin/Pemetrexed; Dose Expansion, Arm L: Mesothelioma

Lenvatinib DRUG

Lenvatinib will be administered orally once daily.

Also known as: LENVIMA®, Lenvanix

Dose Expansion, Arm H: RCC, +Lenvatinib

Paclitaxel DRUG

Paclitaxel will be administered IV QW on Days 1, 8, and 15 of each 21-day cycle until disease progression or prohibitive toxicity (Arm J) and on Days 1, 8, and 15 Q4W until disease progression or prohibitive toxicity (Arm K).

Also known as: Nov-Onxol, Onxol, Paclitaxel Novaplus, Taxol

Dose Expansion, Arm J: Ovarian Cancer; Dose Expansion, Arm K: Triple negative Breast Cancer (TNBC)

Cisplatin DRUG

Cisplatin will be administered IV Q3W.

Also known as: Platinol®, Platinol®-AQ, CDDP

Dose Expansion, Arm L: Mesothelioma

MK-4830A BIOLOGICAL

MK-4830A, a coformulation of MK-4830 800 mg + pembrolizumab 200 mg, will be administered IV Q3W.

Coformulation Phase, Arm N: MK-4830A (Coformulation of MK-4830 + pembrolizumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Dose escalation participants: Has any histologically- or cytologically-confirmed advanced/metastatic solid tumor by pathology report and has received, has been intolerant to, or has been ineligible for all treatment known to confer clinical benefit. Solid tumors of any type are eligible for enrollment
• Has measurable disease by Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1), Response Assessment in Neuro-Oncology (RANO), or modified RECIST (mRECIST) as assessed by the local site investigator/radiology
• Dose Escalation Part C and Back-fill participants: Has 1 or more discrete malignant lesions that are amenable to biopsy
• Demonstrates adequate organ function
• A male participant must agree to use an approved contraception(s) during the treatment period and for at least 180 days after the last dose of study treatment and refrain from donating sperm during this period
• A female participant is eligible to participate if she is not pregnant, not breastfeeding, and either not a woman of childbearing potential (WOCBP) OR if a WOCBP agrees to follow the study contraceptive guidance during the treatment period and for at least 180 days after the last dose of study treatment
• Expansion phase Arm A participants:
• Has histologically or cytologically confirmed metastatic pancreatic adenocarcinoma
• Received at least 1 prior line of therapy and no more than 3 prior lines of systemic therapy
• Expansion phase Arm B participants:
• Has histologically or cytologically confirmed unresectable glioblastoma multiforme (GBM) or its variants
• Has a Karnofsky performance status (KPS) ≥ 70
• Has had no more than 1 prior line of therapy for GBM. Radiation with or without chemotherapy is acceptable as the prior treatment
• Has shown unequivocal evidence for tumor progression by magnetic resonance imaging (MRI) or computed tomography (CT) scan by contrast within 2 weeks prior to randomization
• Has an interval of at least 3 weeks (to randomization) between prior surgical resection (one week for stereotactic biopsy)

You may not qualify if:

• Has had chemotherapy, definitive radiation, or biological cancer therapy within 4 weeks (2 weeks for palliative radiation) prior to the first dose of study therapy, or has not recovered from any adverse events (AEs) that were due to cancer therapeutics administered more than 4 weeks earlier
• Has not recovered from all radiation-related toxicities to Grade 1 or less, requires corticosteroids, and had radiation pneumonitis
• Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years
• Has received any prior immunotherapy and was discontinued from that treatment due to a Grade 3 or higher immune-related AEs
• Has previously had a severe hypersensitivity reaction to treatment with a monoclonal antibody or has a known sensitivity to any component of pembrolizumab and/or chemotherapy agents
• Has an active infection requiring therapy
• Has a history or current interstitial lung disease
• Has a history of noninfectious pneumonitis that required steroids or current pneumonitis
• Has an active autoimmune disease that has required systemic treatment in the past 2 years except vitiligo or resolved childhood asthma/atopy
• Has clinically significant cardiac disease, including unstable angina, acute myocardial infarction within 6 months from Day 1 of study drug administration, or New York Heart Association Class III or IV congestive heart failure
• Has a known history of human immunodeficiency virus (HIV)
• Has a known active hepatitis B or C
• Is taking chronic systemic steroids in doses \>10 mg daily of prednisone or equivalent within 7 days prior to the first dose of trial treatment
• Has not fully recovered from any effects of major surgery without significant detectable infection. Surgical proceduress that required general anesthesia must be completed at least 2 weeks before first study treatment administration. Surgery requiring regional/epidural anesthesia must be completed at least 72 hours before first study treatment administration and participants should be recovered
• Has received a live or live-attenuated virus vaccine within 30 days prior to first dose of study intervention

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (37)

University of California at San Francisco ( Site 0004)

San Francisco, California, 94158, United States

Location

Henry Ford Health System ( Site 0002)

Detroit, Michigan, 48202, United States

Location

Washington University ( Site 0003)

St Louis, Missouri, 63110, United States

Location

John Theurer Cancer Center at Hackensack University Medical Center ( Site 0005)

Hackensack, New Jersey, 07601, United States

Location

Laura and Isaac Perlmutter Cancer Center ( Site 0008)

New York, New York, 10016, United States

Location

Ohio State University Arthur G James Cancer Hospital & Richard J Solove Research Institute ( Site 00

Columbus, Ohio, 43210, United States

Location

South Texas Accelerated Research Therapeutics, LLC (START) ( Site 0001)

San Antonio, Texas, 78229, United States

Location

Utah Cancer Specialists ( Site 0011)

Salt Lake City, Utah, 84106, United States

Location

Seattle Cancer Care Alliance ( Site 0010)

Seattle, Washington, 98109, United States

Location

Liverpool Hospital-Medical Oncology ( Site 0250)

Liverpool, New South Wales, 2170, Australia

Location

Princess Alexandra Hospital ( Site 0253)

Brisbane, Queensland, 4102, Australia

Location

Juravinski Cancer Centre ( Site 0034)

Hamilton, Ontario, L8V 5C2, Canada

Location

The Ottawa Hospital ( Site 0031)

Ottawa, Ontario, K1H 8L6, Canada

Location

Princess Margaret Cancer Centre ( Site 0033)

Toronto, Ontario, M5G 2M9, Canada

Location

The First Hospital of Jilin University ( Site 0803)

Changchun, Jilin, 130021, China

Location

Shanghai Chest Hospital-Oncology department ( Site 0801)

Shanghai, Shanghai Municipality, 200030, China

Location

West China Hospital of Sichuan University ( Site 0804)

Chengdu, Sichuan, 610041, China

Location

Centre Oscar Lambret ( Site 2002)

Lille, Nord, 59000, France

Location

Centre Hospitalier Universitaire de Poitiers ( Site 2000)

Poitiers, Vienne, 86000, France

Location

Hôpital Européen Georges Pompidou ( Site 2003)

Paris, Île-de-France Region, 75015, France

Location

University General Hospital of Heraklion ( Site 0110)

Heraklion, Irakleio, 711 10, Greece

Location

Euromedica General Clinic of Thessaloniki-Oncology Unit ( Site 0112)

Thessaloniki, 546 45, Greece

Location

European Interbalkan Medical Center ( Site 0111)

Thessaloniki, 57001, Greece

Location

Rambam Health Care Campus-Oncology Division ( Site 0042)

Haifa, 3109601, Israel

Location

Rabin Medical Center ( Site 0043)

Petah Tikva, 4941492, Israel

Location

Chaim Sheba Medical Center. ( Site 0044)

Ramat Gan, 5265601, Israel

Location

Sourasky Medical Center ( Site 0041)

Tel Aviv, 6423906, Israel

Location

National Cancer Center Hospital East ( Site 0400)

Kashiwa, Chiba, 2778577, Japan

Location

Japanese Foundation for Cancer Research ( Site 0401)

Tokyo, 135-8550, Japan

Location

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie (

Warsaw, Masovian Voivodeship, 02-781, Poland

Location

Uniwersyteckie Centrum Kliniczne ( Site 0151)

Gdansk, Pomeranian Voivodeship, 80-214, Poland

Location

Wits Clinical Research ( Site 0213)

Johannesburg, Gauteng, 2193, South Africa

Location

The Oncology Centre ( Site 0212)

Durban, KwaZulu-Natal, 4091, South Africa

Location

Cancercare Rondebosch Oncology ( Site 0210)

Cape Town, Western Cape, 7700, South Africa

Location

Severance Hospital Yonsei University Health System ( Site 0300)

Seoul, 03722, South Korea

Location

Instituto Catalan de Oncologia ICO - Hospital Duran i Reynals ( Site 0101)

L'Hospitalet de Llobregat, Barcelona, 08908, Spain

Location

Centro Integral Oncologico Clara Campal START Madrid ( Site 0102)

Madrid, 28050, Spain

Location

Related Publications (1)

• Siu LL, Wang D, Hilton J, Geva R, Rasco D, Perets R, Abraham AK, Wilson DC, Markensohn JF, Lunceford J, Suttner L, Siddiqi S, Altura RA, Maurice-Dror C. First-in-Class Anti-immunoglobulin-like Transcript 4 Myeloid-Specific Antibody MK-4830 Abrogates a PD-1 Resistance Mechanism in Patients with Advanced Solid Tumors. Clin Cancer Res. 2022 Jan 1;28(1):57-70. doi: 10.1158/1078-0432.CCR-21-2160. Epub 2021 Oct 1.

  PMID: 34598945 RESULT

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Conditions

Neoplasms

Interventions

pembrolizumab; Carboplatin; Pemetrexed; lenvatinib; Paclitaxel; Taxes; Cisplatin

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Economics; Health Care Economics and Organizations; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Arms are parallel, except that participants who progress by either clinical or radiographic evaluation on monotherapy with MK-4830 (Dose Escalation, Part B), may switch over into the combination therapy arm of MK-4830 and pembrolizumab (Dose Escalation, Part C), provided they meet eligibility criteria. All arms are non-randomized except Dose Expansion Arms E and F, with randomization of eligible participants between those two arms.

Study Record Dates

• First Submitted: June 11, 2018
• First Posted: June 21, 2018
• Study Start: July 11, 2018
• Primary Completion: September 26, 2025
• Study Completion: September 26, 2025
• Last Updated: October 7, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share

Locations

CA (3); CN (3); ZA (3); GR (3); KR (1); JP (2); AU (2); IL (4); PL (2); US (9); ES (2); FR (3)